Extraction of Prestin-Dependent and Prestin-Independent Components from Complex Motile Responses in Guinea Pig Outer Hair Cells

Electromotility of cochlear outer hair cells (OHC) is associated with conformational changes in the integral membrane protein prestin. We have recently reported that electrical stimulation evokes significant prestin-dependent changes in the length, width, and area of the longitudinal section of OHCs, but not in their volume. In contrast, prestin-independent responses elicited at constant membrane potential are associated with changes in cell length, width, and volume without significant changes in their longitudinal section area. In this report we describe a novel analytical technique, based on a simple theoretical model and continuous measurement of changes in cell length and longitudinal section area, to evaluate the contribution of each one of these mechanisms to the motile response of OHCs. We demonstrate that if the relative change in OHC length (L) during the motile response is expressed as L = A2 × V−1 (with A and V being the relative changes in longitudinal section area and volume, respectively), A2 will describe the contribution of the prestin-dependent mechanism whereas V−1 will describe the contribution of the prestin-independent mechanism. Thus, relative changes in any two of these cellular morphological parameters (L, A, or V) would be necessary and sufficient for characterizing any OHC motile response. This simple approach provides access to information previously unavailable, and may become a novel and important tool for increasing our understanding of the cellular and molecular mechanisms of OHC motility.